Within the context of a continuing broad interest in leukocyte proliferation and differentiation, specific studies will attempt to: 1) Clarify the mechanisms involved in both the suppression and initiation of human lymphocyte proliferation in short-term cultures; and 2) further delineate the role of chromosome abnormalities in the disordered proliferation of leukocytes in vivo in human preleukemia and chronic leukemia. For the studies of lymphocyte suppression (1), a feeder layer culture system will be used to assay human suppressor lymphocytes generated in mitogen-stimulated bulk cultures, considering both their specific (immunological) and non-specific (chalone) effects. For the studies of lymphocyte "triggering", the cellular subpopulations and interactions involved in the mitogenic response to a calcium ionophore will be compared with the effects of lectin mitogens, and the findings correlated with a companion study of the early molecular events. For the chromosome studies (2), new banding techniques will be used to expand long-term studies concerned with the prognostic value of chromosomally abnormal hemic cell clones in preleukemia, chronic granulocytic leukemia, and chronic lymphocytic leukemia, and the significance of these visible genetic changes in the evolution of human neoplastic cell populations.